The present invention relates to ubiquinone compositions that can be used to deliver ubiquinones to a host and to methods of making such compositions.
Ubiquinones, such as Coenzyme Q10 (hereinafter “CoQ10”), are essentially a vitamin-like substance. CoQ10 is found in small amounts in a wide variety of foods and is synthesized in all tissues. The biosynthesis of CoQ10 from the amino acid tyrosine is a multi-stage process requiring eight vitamins and several trace elements. Co-enzymes are co-factors upon which comparatively large and complex enzymes depend for their function. CoQ10 is the co-enzyme for at least three mitochondrial enzymes (complexes I, II and III) as well as enzymes in other parts of the cell.
Mitochondrial enzymes of the oxidative phosphorylation pathway are essential for the production of adenosine triphosphate (ATP), upon which all cellular functions depend. CoQ10 plays a critical role in the sequential transfer of electrons in the mitochondrion.
In addition to electron transport in the mitochondrion, CoQ10 has also been found to be important in the prevention of cellular-free radical damage, oxygenation at the cellular level, as well as other benefits.
Studies have demonstrated that sufficient levels of CoQ10 promote optimal cell function in the human body. Significantly decreased levels of CoQ10 have been noted in a wide variety of diseases in both animal and human studies. CoQ10 deficiency may be caused by insufficient dietary CoQ10, impairment in CoQ10 biosynthesis, excessive utilization of CoQ10 by the body, or any combination.
Various CoQ10 formulations and methods of administration have been evaluated in clinical settings and demonstrate the potential and versatility of CoQ10 compositions for a broad spectrum of disorders. CoQ10 has been labeled a “breakthrough” drug in congestive heart failure—showing clinical benefit in 75% of patients (Greenberg and Frishman, J. Clin. Pharmacol, 30: 596-608 (1990); Oda, Drugs Exp. Clin. Res., 11: 557-76 (1985)). CoQ10 has been used to combat the effects of muscular dystrophy, producing clinical benefit in a subpopulation of patients with Duchenne form (Folkers, et al., Proc. Natl. Acad. Sci. U.S.A., 82: 4513-6 (1985)). CoQ10 has been successfully utilized to battle periodontal disease (Wilkinson, et al., Res. Commun. Chem. Pathol. Pharmacol., 14: 715-9 (1976)). CoQ10 has been implicated in the reduction in toxicity of chemotherapeutic drugs, e.g., cardiac toxicity of adriamycin (R. Ogura, et al., J. Nutr. Sci. Vitaminol., 28: 329-34 (1982)). CoQ10 has been successfully implemented in the correction of drug-induced deficiencies, e.g., psychotherapeutic, diabetes and beta-blocker drugs (Katsumoto and Inoue, Jpn. Circ. J, 47: 356-62 (1983)). CoQ10 has been used in immune restoration, e.g., aging, AIDS, allergies (Suzuki, et al., Jpn. J. Surg., 16: 152-5 (1986); Folkers, et al., Res. Commun. Chem. Pathol. Pharmacol., 38: 335-8 (1982); Folkers, et al., Biochem. Biophys. Res. Commun., 193: 88-92 (1993)).
CoQ10 supplementation can be beneficial at any age, but due to statin-types of hyperlipidimia medications removing naturally occurring CoQ10 from the body and the age related depletion of the body's natural resources of CoQ10 by age 35, CoQ10 supplementation may be most beneficial to those above age 35. Studies have shown that a decrease in CoQ10 levels by 25% results in an inability of the body to produce enough cellular energy to remain healthy. A decline of 75% in CoQ10 can be fatal.
Ubiquinones, including CoQ10, are essentially insoluble in aqueous media. This insolubility may be attributed to the long hydrocarbon isoprenoid side chain which provides the molecule with its extremely lipophilic characteristics. These characteristics, among other effects, appear to be the source of the very slow absorption rates of the molecule. Pharmacokinetic data has demonstrated that intestinal absorption of ubiquinones is slow and ineffective in human subjects. By way of example, after administration of CoQ10 there is a lag time of about 1 hour before increased plasma levels of CoQ10 can be detected. A second absorption peak appears after about 24 hours. Approximately seven days of administration is required to achieve maximum steady-state plasma levels. Furthermore, absorption of orally administered CoQ10 is variable and generally in the range of only about 2-5%.
Others have primarily focused on the production of the fatty emulsion of CoQ10 in order to increase bioavailability and stability of CoQ10. All of these formulations contain emulsifying agents. In fact, none of these CoQ10 formulations are free of detergents or surfactants. Further, because of the nature of the oil emulsion, these formulations provide limited bioavailability in concentrations of CoQ10 to the desired delivery sites in the body. Generally, oil formulations are highly viscous formulations with relatively low CoQ10 concentration and accumulates slowly into cell membranes; commonly no more than 10 mg per ml. More importantly, emulsions are slowly absorbed and accumulate at low levels in cells.
Therefore, there remains a need for ubiquinone-containing compositions, for example compositions containing CoQ10, with improved stability and bioactivity characteristics.